Background/Objectives: Circulating tumour DNA (ctDNA) assays enable non-invasive assessment of tumour burden and treatment response in oncology. However, quantitative ctDNA outputs (such as variant allele frequency, tumour fraction, and aggregate burden scores) remain difficult to interpret and compare across platforms. This evidence-mapping review evaluates current quantitative reporting approaches in pancreatic ductal adenocarcinoma (PDAC) and examines the potential role of KRAS mutant ctDNA as a biologically grounded reference metric. Methods: A systematic literature search was conducted across PubMed/MEDLINE and Scopus to identify studies reporting quantitative ctDNA metrics in PDAC. Eligible studies included those measuring plasma KRAS mutations and/or reporting variant allele frequency, tumour fraction, or multi-locus aggregate metrics. Additional relevant primary studies identified through broader manual searching of PubMed were assessed against the same prespecified eligibility and classification criteria before inclusion. Data were synthesised narratively, focusing on reporting frameworks, units of measurement, assay characteristics, and the interpretability of quantitative outputs across platforms. Results: Substantial heterogeneity was observed in ctDNA quantification methods and reporting standards. Ratio-based metrics such as variant allele frequency and tumour fraction were commonly used but varied according to assay design, plasma input volume, and background cell-free DNA levels. Few studies reported absolute mutant molecule counts per unit volume. Given that approximately 90–95% of PDACs harbour truncal activating KRAS mutations, plasma KRAS was consistently represented across platforms and demonstrated potential as a shared quantitative anchor. Limited standardisation was noted in distinguishing detectability from quantifiability based on sampling depth and counting statistics. Conclusions: Current ctDNA reporting in PDAC lacks a shared quantitative reference, limiting cross-study comparability. Reporting KRAS mutant molecules per millilitre and adopting an assay-agnostic framework distinguishing detection from quantification may improve interpretability, support harmonisation across platforms, and facilitate cumulative learning in pancreatic cancer ctDNA research.
Croagh et al. (Tue,) studied this question.